neurobiology of addiction presentation [autosaved]
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Microsoft PowerPoint - Neurobiology of Addiction presentation
[Autosaved].pptx• Identify the neurotransmitter systems that
mediate the reinforcing effects of drugs
• Explain the fundamental changes that occur in the brain with addiction
What is Addiction?
• Changes in the DSM • IV-TR differentiated between abuse and
dependence • 5 clusters it as Substance Use Disorder
• The term “Addiction” is sloppy • Chocolate • TV shows • Exercise
Degrees of Use
• Addiction
• A person may fluctuate or “get stuck” in one of these categories
Why do we use?
• Escape, Relax
• Relieve boredom
• Does abuse evolve into addiction? “Pre-Addiction?” • Some people are “instantly addicted”
• Some people become addicted during the first year of use
• Some abusers never become addicted
• Estimated lifetime prevalence risk
• >22 million Americans have abuse/addiction problem
• No discrimination as to race, gender, socioeconomic status, age
• Tobacco, Alcohol and Illegal drugs
• $524 billion a year spent
• 15- 20% of patients have alcohol/ drug abuse and addiction disorders
• 20% of Medicaid hospital costs and 25% of Medicare hospital costs are associated with substance abuse
• Economic burden is twice as much as any other disease affecting the brain
Addiction/ Brain Disease
• Compulsion to seek and take a drug/ substance
• Loss of control in limiting the intake of the substance
• Negative emotional and/or physiological state if access to the substance is prevented
• Progressive disease with chronic relapses
• Shifts from an impulse control disorder involving positive reinforcement to a compulsive disorder involving negative reinforcement
What are we really talking about today? (Neurobiology)
• What happens in the brain to cause an addicted person to lose control? Especially when there is serious drug related consequences?
• Why are relapses in drug use so common, even in people who have years of abstinence?
Movie Clip
• Losing Isaiah
Brain Basics
• The Brain… • Tells us who we are, what we are doing, what
we have done
• Plasticity
• Excitatory and Inhibitory influences
• Action potentials = action
• Act at presynaptic terminal or postsynaptic membrane on the neurotransmitter receptor
Neuroimaging and Neurobiology
• Measure local concentration of drug at binding sites
• Estimate receptor occupancy based on competitive binding assays
• Evaluate the effects of drugs on neurotransmitters
• Investigate activity of enzymes that metabolize drugs
Neurobiology of Addiction
• Most progress derived from study of animal models of addiction
• Focused on specific drugs
• Positive effects
• Negative effects
• Craving stage
• Impulsivity
• Increase in sense of tension or arousal before committing an impulsive act
• Pleasure, gratification or relief at the time of committing the act
• Regret, self-reproach, or guilt following the act
• Compulsivity
• Relief from stress by performing the behavior
Stages of Addiction
• Progresses from impulsivity to compulsivity in a 3 stage cycle:
• Binge/ intoxication
• Impulsivity and Compulsivity coexist in different stages of addiction cycle
Binge/ Intoxication Stage
• Positive Reinforcing Effects
Nucleus Accumbens • Critical to learning, reward and motivation
• Everyday activities produce increases in the Nucleus Accumbens
• Food
• Relationships
• Sex
• Pleasurable feelings reinforce the behavior so it will be repeated
Other Neurotransmitters Involved
• Serotonin • Mood, sleep
• Cannabinoids • Mediation of synaptic traffic
• Norepinephrine • Arousal, dreaming, moods, blood pressure, heart rate
• Acetylcholine • Muscle contraction
• Corticotropin Releasing Factor (CRF) • Stress
Thus, drugs are associated with neurotransmitters
• Assume that genetics + drug use = dysregulations of neurotransmitter systems
• As people use, the drugs “connect” to specific dysregulated neurotransmitter system
• May be why people have “drugs of choice”
• Multiple dysregulations could explain co-dependence on several drugs
Drugs of Choice and Neurotransmitters
• Amphetamines, cocaine, ETOH
• Integration of arousal-stress systems with reward pathway
• Extended Amygdala
• Nucleus Accumbens
• Decreases in dopaminergic transmission
• Decreased GABA transmission
• Between-system adaptation
• Chronic activation of the reward system results in dysregulation of other neurochemical systems
• Recruitment of the brain stress system (CRF)
• Synaptic plasticity
• Tolerance develops • Rewarding capacity decreases • Consumption of larger amounts of drugs does not increase reward • Motivation for the use increases
• Withdrawal Symptoms • Anxiety • Pain • Sleep disturbance • Loss of motivation for natural rewards • Malaise • Dysphoria • Irritability
• Compromised social, occupational or recreational activities • Craving
Stage 3: Preoccupation/ Anticipation
• Orbitofrontal cortex changes
• Stress
• Craving
• Relapse
Pickles
• Once a cucumber becomes a pickle, it is no longer a cucumber
• Some cucumbers never become pickles
• Why do some people become addicted to drugs while others do not?
• Vulnerability
Genetics
is genetic
environmental factors
• Substance abusers experience higher rates of other comorbid mental illness compared to the general population
• Psychosis
• Depression
• Anxiety
• Witnessing violence
• Biological and behavioral components
• Recovery is long term • Often requires repeated episodes of treatment
• Relapses occur • During or after treatment
• Treatment may need to be reinstated or adjusted
Normal Control Meth user
(36 months abstinent)
• Research
• Education
• Erase the stigma of addiction as a poor choice, narcissistic, antisocial behavior
• Understand the severity and chronicity of the brain disease
Thank You!
References • American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders Fifth Edition DSM-5.
• Brown, R.M., Kupchik, Y.M., & Kalivas, P.W. (2013). The story of glutamate in drug addiction and of N-acetylcystene as potential pharmacotherapy. JAMA Psychiatry 70(9):895-897.
• Carter, A., Hall, W. & Nutt, D. (2011). The neurobiology of addiction. Addiction Neurobiology: Ethical and Social Implications pp. 29-50.
• Erickson, C. (2009). Understanding addiction: Basic science information: Addiction Science Research and Education Center. University of Texas College of Pharmacy. Retrieved from www.utexas.edu/research/asrec/addiction.html
• Fowler, J.S., Volkow, N.D., Kassed, C.A., & Cheng, L. (April, 2007). Imaging the addicted human brain. Science and Practice Perspectives pp. 4-15.
• Gardner, E.L. (2012). Neurobiology of addiction. American Society of Addiction Medicine. Retrieved www.drugabuse.gov
• Hyman, S. E. & Malenka, R.C. (2001). Addiction and the brain: The neurobiology of compulsion and its persisitence. Nature Reviews/ Neuroscience 2: 695-703.
• Koob, G.F. & simon, E.J. (2010). The neurobiology of addiction: Where we have been and where we are going. Journal of
Drug Issues 39(1): 115-132.
• Lingford-Hughes, A. & Nutt, D. (2003) Neurobiology of addiction and implications for treatment. The British Journal of Psychiatry 182:97-100.
• National Institute on Drug Abuse (NIDA). (2010). Drugs, brains and behavior. The science of addiction. National Institutes
of Health. www.drugabuse.gov
• Roberts, A.J. & Koob, G.F. (1997). The neurobiology of addiction: An overview. Alcohol Health and Research World 21(2): 101-106.
• San Francisco Chronicle. (October 19, 1998). Broader treatment may aid drug addicts.
• Sinha, R. (2013). The clinical neurobioloby of drug craving. Current Opinion in Neurobiology 23: 649-654.
• Trigo, J.M, Martin-Garcia, E., Berrendero, F., Robledo, P. & Maldonado, R. (2010). The endogenous opioid system: A common substrate in drug addiction. Drug and Alcohol Dependence 108(3): 183-194.
• Wise, R.A. & Koob, G.F. (2014). The development and maintenance of drug addiction. Neuropsychopharmacology 39:254- 262.
Post Presentation Questions
2. Addiction is a relapsing disorder with roots in ______________ and __________________.
3. Name the 3 stages of addiction.
4. What neurotransmitter is associated with the Reward Pathway?
Post Presentation Answers
1. Define drug addiction. Compulsion to seek and take drugs despite negative consequences; loss of control in limiting intake; if access is prevented, negative emotional and physical state occur
2. Addiction is a relapsing disorder with roots in Impulsivity and Compulsivity.
3. Name the 3 stages of addiction. Binge/Intoxication; Withdrawal; Preoccupation/ Anticipation
• Explain the fundamental changes that occur in the brain with addiction
What is Addiction?
• Changes in the DSM • IV-TR differentiated between abuse and
dependence • 5 clusters it as Substance Use Disorder
• The term “Addiction” is sloppy • Chocolate • TV shows • Exercise
Degrees of Use
• Addiction
• A person may fluctuate or “get stuck” in one of these categories
Why do we use?
• Escape, Relax
• Relieve boredom
• Does abuse evolve into addiction? “Pre-Addiction?” • Some people are “instantly addicted”
• Some people become addicted during the first year of use
• Some abusers never become addicted
• Estimated lifetime prevalence risk
• >22 million Americans have abuse/addiction problem
• No discrimination as to race, gender, socioeconomic status, age
• Tobacco, Alcohol and Illegal drugs
• $524 billion a year spent
• 15- 20% of patients have alcohol/ drug abuse and addiction disorders
• 20% of Medicaid hospital costs and 25% of Medicare hospital costs are associated with substance abuse
• Economic burden is twice as much as any other disease affecting the brain
Addiction/ Brain Disease
• Compulsion to seek and take a drug/ substance
• Loss of control in limiting the intake of the substance
• Negative emotional and/or physiological state if access to the substance is prevented
• Progressive disease with chronic relapses
• Shifts from an impulse control disorder involving positive reinforcement to a compulsive disorder involving negative reinforcement
What are we really talking about today? (Neurobiology)
• What happens in the brain to cause an addicted person to lose control? Especially when there is serious drug related consequences?
• Why are relapses in drug use so common, even in people who have years of abstinence?
Movie Clip
• Losing Isaiah
Brain Basics
• The Brain… • Tells us who we are, what we are doing, what
we have done
• Plasticity
• Excitatory and Inhibitory influences
• Action potentials = action
• Act at presynaptic terminal or postsynaptic membrane on the neurotransmitter receptor
Neuroimaging and Neurobiology
• Measure local concentration of drug at binding sites
• Estimate receptor occupancy based on competitive binding assays
• Evaluate the effects of drugs on neurotransmitters
• Investigate activity of enzymes that metabolize drugs
Neurobiology of Addiction
• Most progress derived from study of animal models of addiction
• Focused on specific drugs
• Positive effects
• Negative effects
• Craving stage
• Impulsivity
• Increase in sense of tension or arousal before committing an impulsive act
• Pleasure, gratification or relief at the time of committing the act
• Regret, self-reproach, or guilt following the act
• Compulsivity
• Relief from stress by performing the behavior
Stages of Addiction
• Progresses from impulsivity to compulsivity in a 3 stage cycle:
• Binge/ intoxication
• Impulsivity and Compulsivity coexist in different stages of addiction cycle
Binge/ Intoxication Stage
• Positive Reinforcing Effects
Nucleus Accumbens • Critical to learning, reward and motivation
• Everyday activities produce increases in the Nucleus Accumbens
• Food
• Relationships
• Sex
• Pleasurable feelings reinforce the behavior so it will be repeated
Other Neurotransmitters Involved
• Serotonin • Mood, sleep
• Cannabinoids • Mediation of synaptic traffic
• Norepinephrine • Arousal, dreaming, moods, blood pressure, heart rate
• Acetylcholine • Muscle contraction
• Corticotropin Releasing Factor (CRF) • Stress
Thus, drugs are associated with neurotransmitters
• Assume that genetics + drug use = dysregulations of neurotransmitter systems
• As people use, the drugs “connect” to specific dysregulated neurotransmitter system
• May be why people have “drugs of choice”
• Multiple dysregulations could explain co-dependence on several drugs
Drugs of Choice and Neurotransmitters
• Amphetamines, cocaine, ETOH
• Integration of arousal-stress systems with reward pathway
• Extended Amygdala
• Nucleus Accumbens
• Decreases in dopaminergic transmission
• Decreased GABA transmission
• Between-system adaptation
• Chronic activation of the reward system results in dysregulation of other neurochemical systems
• Recruitment of the brain stress system (CRF)
• Synaptic plasticity
• Tolerance develops • Rewarding capacity decreases • Consumption of larger amounts of drugs does not increase reward • Motivation for the use increases
• Withdrawal Symptoms • Anxiety • Pain • Sleep disturbance • Loss of motivation for natural rewards • Malaise • Dysphoria • Irritability
• Compromised social, occupational or recreational activities • Craving
Stage 3: Preoccupation/ Anticipation
• Orbitofrontal cortex changes
• Stress
• Craving
• Relapse
Pickles
• Once a cucumber becomes a pickle, it is no longer a cucumber
• Some cucumbers never become pickles
• Why do some people become addicted to drugs while others do not?
• Vulnerability
Genetics
is genetic
environmental factors
• Substance abusers experience higher rates of other comorbid mental illness compared to the general population
• Psychosis
• Depression
• Anxiety
• Witnessing violence
• Biological and behavioral components
• Recovery is long term • Often requires repeated episodes of treatment
• Relapses occur • During or after treatment
• Treatment may need to be reinstated or adjusted
Normal Control Meth user
(36 months abstinent)
• Research
• Education
• Erase the stigma of addiction as a poor choice, narcissistic, antisocial behavior
• Understand the severity and chronicity of the brain disease
Thank You!
References • American Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders Fifth Edition DSM-5.
• Brown, R.M., Kupchik, Y.M., & Kalivas, P.W. (2013). The story of glutamate in drug addiction and of N-acetylcystene as potential pharmacotherapy. JAMA Psychiatry 70(9):895-897.
• Carter, A., Hall, W. & Nutt, D. (2011). The neurobiology of addiction. Addiction Neurobiology: Ethical and Social Implications pp. 29-50.
• Erickson, C. (2009). Understanding addiction: Basic science information: Addiction Science Research and Education Center. University of Texas College of Pharmacy. Retrieved from www.utexas.edu/research/asrec/addiction.html
• Fowler, J.S., Volkow, N.D., Kassed, C.A., & Cheng, L. (April, 2007). Imaging the addicted human brain. Science and Practice Perspectives pp. 4-15.
• Gardner, E.L. (2012). Neurobiology of addiction. American Society of Addiction Medicine. Retrieved www.drugabuse.gov
• Hyman, S. E. & Malenka, R.C. (2001). Addiction and the brain: The neurobiology of compulsion and its persisitence. Nature Reviews/ Neuroscience 2: 695-703.
• Koob, G.F. & simon, E.J. (2010). The neurobiology of addiction: Where we have been and where we are going. Journal of
Drug Issues 39(1): 115-132.
• Lingford-Hughes, A. & Nutt, D. (2003) Neurobiology of addiction and implications for treatment. The British Journal of Psychiatry 182:97-100.
• National Institute on Drug Abuse (NIDA). (2010). Drugs, brains and behavior. The science of addiction. National Institutes
of Health. www.drugabuse.gov
• Roberts, A.J. & Koob, G.F. (1997). The neurobiology of addiction: An overview. Alcohol Health and Research World 21(2): 101-106.
• San Francisco Chronicle. (October 19, 1998). Broader treatment may aid drug addicts.
• Sinha, R. (2013). The clinical neurobioloby of drug craving. Current Opinion in Neurobiology 23: 649-654.
• Trigo, J.M, Martin-Garcia, E., Berrendero, F., Robledo, P. & Maldonado, R. (2010). The endogenous opioid system: A common substrate in drug addiction. Drug and Alcohol Dependence 108(3): 183-194.
• Wise, R.A. & Koob, G.F. (2014). The development and maintenance of drug addiction. Neuropsychopharmacology 39:254- 262.
Post Presentation Questions
2. Addiction is a relapsing disorder with roots in ______________ and __________________.
3. Name the 3 stages of addiction.
4. What neurotransmitter is associated with the Reward Pathway?
Post Presentation Answers
1. Define drug addiction. Compulsion to seek and take drugs despite negative consequences; loss of control in limiting intake; if access is prevented, negative emotional and physical state occur
2. Addiction is a relapsing disorder with roots in Impulsivity and Compulsivity.
3. Name the 3 stages of addiction. Binge/Intoxication; Withdrawal; Preoccupation/ Anticipation